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      Serum biomarkers of delirium in the elderly: a narrative review

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          Abstract

          Delirium after surgery and in the intensive care unit (ICU) remains a challenge for patients, families, and caregivers. Over the years, many promising biomarkers have been investigated as potential instruments for risk stratification of delirium. This review aimed to identify and assess the clinical usefulness of candidate serum biomarkers associated with hospital delirium in patients aged 60 years and older. We performed a time-unlimited review of publications indexed in PubMed, Cochrane, Embase, and MEDLINE databases until June 2019 that evaluated baseline and/or longitudinal biomarker measurements in patients suffering from delirium at some point during their hospital stay. A total of 32 studies were included in this review reporting information on 7610 patients. Of these 32 studies, twenty-four studies reported data from surgical patients including four studies in ICU cohorts, five studies reported data from medical patients (1026 patients), and three studies reported data from a mixed cohort (1086 patients), including one study in an ICU cohort. Findings confirm restricted clinical usefulness to predict or diagnose delirium due to limited evidence on which biomarkers can be used and limited availability due to non-routine use.

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          Delirium in older persons.

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            One-year health care costs associated with delirium in the elderly population.

            While delirium has been increasingly recognized as a serious and potentially preventable condition, its long-term implications are not well understood. This study determined the total 1-year health care costs associated with delirium. Hospitalized patients aged 70 years and older who participated in a previous controlled clinical trial of a delirium prevention intervention at an academic medical center between 1995 and 1998 were followed up for 1 year after discharge. Total inflation-adjusted health care costs, calculated as either reimbursed amounts or hospital charges converted to costs, were computed by means of data from Medicare administrative files, hospital billing records, and the Connecticut Long-term Care Registry. Regression models were used to determine costs associated with delirium after adjusting for patient sociodemographic and clinical characteristics. During the index hospitalization, 109 patients (13.0%) developed delirium while 732 did not. Patients with delirium had significantly higher unadjusted health care costs and survived fewer days. After adjusting for pertinent demographic and clinical characteristics, average costs per day survived among patients with delirium were more than 2(1/2) times the costs among patients without delirium. Total cost estimates attributable to delirium ranged from $16 303 to $64 421 per patient, implying that the national burden of delirium on the health care system ranges from $38 billion to $152 billion each year. The economic impact of delirium is substantial, rivaling the health care costs of falls and diabetes mellitus. These results highlight the need for increased efforts to mitigate this clinically significant and costly disorder.
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              Delirium is independently associated with poor functional recovery after hip fracture.

              To evaluate the role of delirium in the natural history of functional recovery after hip fracture surgery, independent of prefracture status. Prospective cohort study. Orthopedic surgery service at a large academic tertiary hospital, with follow-up extending into rehabilitation hospitals, nursing homes, and the community. One hundred twenty-six consenting subjects older than 65 years (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture. Detailed assessment at enrollment to ascertain prefracture status through interviews with the patient and designated proxy and review of the medical record. Interviews included administration of standardized instruments (Activities of Daily Living (ADL) Scale, Blessed Dementia Rating Scale, Delirium Symptom Interview) and assessment of ambulation, and prefracture living situation. Medical comorbidity, the nature of the hip fracture, and the surgical repair were obtained from the medical record. All subjects underwent daily interviews for the duration of the hospitalization, including the Mini-Mental State Examination and Delirium Symptom Interview, and delirium was diagnosed using the Confusion Assessment Methods algorithm. Patients and proxies were recontacted 1 and 6 months after fracture, and underwent interviews similar to those at enrollment to determine death, persistent delirium, decline in ADL function, decline in ambulation, or new nursing home placement. Delirium occurred in 52/126 (41%) of patients, and persisted in 20/52 (39%) at hospital discharge, 15/52 (32%) at 1 month, and 3/52 (6%) at 6 months. Patients aged 80 years or older, and those with prefracture cognitive impairment, ADL functional impairment, and high medical comorbidity were more likely to develop delirium. However, after adjusting for these factors, delirium was still significantly associated with outcomes indicative of poor functional recovery 1 month after hip fracture: ADL decline (odds ratio (OR) = 2.6; 95% confidence interval (95% CI), 1.1- 6.1), decline in ambulation (OR = 2.6; 95% CI, 1.03-6.5), and death or new nursing home placement (OR = 3.0; 95% CI, 1.1-8.4). Patients whose delirium persisted at 1 month had worse outcomes than those whose delirium had resolved. Delirium is common, persistent, and independently associated with poor functional recovery 1 month after hip fracture even after adjusting for prefracture frailty. Further research is necessary to identify the mechanisms by which delirium contributes to poor functional recovery, and to determine whether interventions designed to prevent or reduce delirium can improve recovery after hip fracture.
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                Author and article information

                Contributors
                katharina.toft@gmail.com
                janna.tontsch@stud.unibas.ch
                salim.abdelhamid@usb.ch
                luzius.steiner@usb.ch
                martin.siegemund@usb.ch
                +41-61-265-7254 , alexa.hollinger@usb.ch
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                1 July 2019
                1 July 2019
                2019
                : 9
                : 76
                Affiliations
                [1 ]Department for Anesthesia, Intensive Care and Emergency Medicine, See-Spital, Horgen, Kilchberg, Switzerland
                [2 ]Institute for Anesthesia and Intensive Care, Hirslanden Klinik Zurich, Zurich, Switzerland
                [3 ]GRID grid.410567.1, Department for Intensive Care, , University Hospital Basel, ; Basel, Switzerland
                [4 ]ISNI 0000 0004 1937 0642, GRID grid.6612.3, Medical Faculty of the University of Basel, ; Basel, Switzerland
                [5 ]GRID grid.410567.1, Department for Anesthesia, Prehospital Emergency Medicine and Pain Therapy, , University Hospital Basel, ; Basel, Switzerland
                Author information
                http://orcid.org/0000-0001-6799-1652
                Article
                548
                10.1186/s13613-019-0548-1
                6603109
                31263968
                61dddb8e-4f3e-46cc-b391-247d0efaca61
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 6 June 2019
                : 20 June 2019
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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